A Stereochemically-Constrained Enkephalin Analog: $\alpha-{Aminoisobutyryl}^2$ ${methionine}^5$ enkephalinamide

The discovery that the pentapeptides Tyr-Gly-Gly-Phe-Met (${Met}^5$-enkephalin) and Tyr-Gly-Gly-Phe-Leu (${Leu}^5$-enkephalin), present in the mammalian central nervous system [1,2], possess opioid activity has stimulated considerable interest in their conformations [3-15]. The enkephalins have been shown to bind to the opiate receptor in brain and displace naloxone, a powerful opiate antagonist [16]. The structures of the enkephalins have been the subject of a number of spectroscopic and theoretical investigations. There have been attempts to build a structural model for the pentapeptides that mimics the essential features of the morphine molecule [8-11]. From these studies conflicting suggestions have emerged about the low energy conformation of enkephalins and also the possible conformation of the pentapeptides at the opiate receptor site